Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration

B Nelson; S Nishimura; H Kanuka; E Kuranaga; M Inoue; G Hori; H Nakahara; M Miura

doi:10.1038/sj.cdd.4401635

Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration

Cell Death Differ. 2005 Aug;12(8):1115-23. doi: 10.1038/sj.cdd.4401635.

Authors

B Nelson¹, S Nishimura, H Kanuka, E Kuranaga, M Inoue, G Hori, H Nakahara, M Miura

Affiliation

¹ Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

PMID: 15861189
DOI: 10.1038/sj.cdd.4401635

Abstract

Transcriptional dysregulation as a result of sequestration of essential transcription factors into protein aggregates formed by polyglutamine (polyQ) expansions can lead to late-onset progressive neurodegeneration. DNA microarray analysis of Drosophila expressing polyQ in the compound eye over time revealed large numbers of transcriptional changes at the earliest stages of the disease including repression of the transient receptor potential calcium channels in a polyQ-induced cell death specific manner. While significant differences in expression profiles were found between the Drosophila compound eye and polyQ-sensitive neural cells, a number of possible key overlapping regulators were extracted. Among these, PDK1 was shown to act as a mediator for polyQ-toxicity, suggesting the involvement of the TOR pathway in polyQ-induced neurodegeneration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3-Phosphoinositide-Dependent Protein Kinases
Aging / genetics
Aging / metabolism
Animals
Base Sequence
Cells, Cultured
Drosophila Proteins / genetics
Drosophila Proteins / metabolism
Drosophila Proteins / physiology*
Drosophila melanogaster / genetics*
Drosophila melanogaster / metabolism
Gene Expression Regulation / physiology
Neurodegenerative Diseases / genetics*
Neurodegenerative Diseases / metabolism*
Neurons / metabolism
Neurons / physiology
Oligonucleotide Array Sequence Analysis
Peptides / genetics
Peptides / metabolism*
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / physiology*
Plasmids / genetics
Protein Kinases
Protein Serine-Threonine Kinases / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Protein S6 Kinases / metabolism
Signal Transduction
TOR Serine-Threonine Kinases
Transcription, Genetic / physiology

Substances

Drosophila Proteins
Peptides
polyglutamine
Protein Kinases
target of rapamycin protein, Drosophila
3-Phosphoinositide-Dependent Protein Kinases
Protein Serine-Threonine Kinases
Ribosomal Protein S6 Kinases
TOR Serine-Threonine Kinases